1. Field of the Invention
This invention relates to spherical granules and the production method thereof and, in particular, to spherical granules comprising lactose, which are useful excipients for medicines and foods.
2. Related Art Statement
Recentlly, controlled release techniques for medicines (e.g. sustained release drugs and enteric coating drugs) have made remarkable progress. Among them, there is widely used a release control method, wherein the surface of uniform-size spherical particles is coated with a medicinal layer and a release control layer, and, if necessary, several kinds of coated particles having different thickness of a coating layer from one another are put into a capsule to obtain a preparation having more uniform sustained release.
Usually, the spherical particles used in this method are made of sucrose or a mixture of sucrose and starch. To obtain the spherical particles, the nuclei of the crystalline sucrose are fed into a centrifugal fluidized granulating apparatus, and, then, fine powder of sucrose or a mixture of sucrose and starch is sprayed into the granulating apparatus to be coated on the nuclei while sucrose solution or a mixed solution of sucrose and starch is sprayed as a binder.
However, the conventional spherical particles made of sucrose or sucrose and starch mixture and the conventional production method have the following deficiencies.
(1) The water-solubility of sucrose Is very high, and, therefore, use of an aqueous liquid to coat the surface of the spherical particles with medicinal and release control layers may cause the particles to agglomerate with one another and stick to the wall of the granulating apparatus. Furthermore, at the time of application of the medicinal preparation made with this nuclei, sucrose may come out of the preparation as water infiltrates, thereby the preparation losing its shape and sustained-release property before attaining its object. PA0 (2) The calorific value of sucrose may be disadvantageous to diabetics.
In order to eliminate these deficiencies, the use of spherical particles made singly of crystalline cellulose was suggested for release control purposes (Summary of the lectures presented at the 7th Symposium on Preparation and Particle Design; Oct. 24 and 25, 1990, p.89).
Although spherical particles made of crystalline cellulose have eliminated the above-mentioned deficiencies of the spherical particles made of sucrose or a mixture of sucrose and starch, they pose new and difficult problems of their own. Since crystalline cellulose Is insoluble in water, it takes a long time to break down, and sometimes the release-control layer prevents complete release of the medicine or the spherical particles are excreted without being digested arousing patients' suspiction on the effectiveness of the preparation.
Another improved method using lactose granules has also been proposed, and a preparing method and physical properties of such spherical granules have been disclosed in Miyake et al. "Spheronizing Mechanism and Properties of Spherical Granules", YAKUZAIGAKU (Pharmacology) Vol.33, No.4 (1973) pp.161-165.
However, the lactose granules obtained by the method described in the above article were far from spherical, the aspect ratio (long diameter/short diameter ratio) of the granules being 1.3 or more, and, as aggregate, the bulk density was 0.6 g/ml or less, and, therefore, It lacks free flowing property and it is difficult to fill up a capsule with correct quantity.
The purpose of the present invention is to provide new spherical granules that are free of the above-mentioned deficiencies of the spherical particles made of sucrose or a mixture of sucrose and starch, crystalline cellulose or lactose, and to provide a production method thereof.